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Cell Host Microbe. 2015 Sep 9;18(3):307-19. doi: 10.1016/j.chom.2015.07.006. Epub 2015 Aug 20.

Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs.

Author information

1
Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA.
2
Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.
3
Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
4
Departments of Pathology and Laboratory Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.
5
Department of Microbiology, University of Iowa School of Medicine, Iowa City, IA 52240, USA.
6
Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195, USA; Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA. Electronic address: singhpr@u.washington.edu.

Abstract

Bacterial lineages that chronically infect cystic fibrosis (CF) patients genetically diversify during infection. However, the mechanisms driving diversification are unknown. By dissecting ten CF lung pairs and studying ∼12,000 regional isolates, we were able to investigate whether clonally related Pseudomonas aeruginosa inhabiting different lung regions evolve independently and differ functionally. Phylogenetic analysis of genome sequences showed that regional isolation of P. aeruginosa drives divergent evolution. We investigated the consequences of regional evolution by studying isolates from mildly and severely diseased lung regions and found evolved differences in bacterial nutritional requirements, host defense and antibiotic resistance, and virulence due to hyperactivity of the type 3 secretion system. These findings suggest that bacterial intermixing is limited in CF lungs and that regional selective pressures may markedly differ. The findings also may explain how specialized bacterial variants arise during infection and raise the possibility that pathogen diversification occurs in other chronic infections characterized by spatially heterogeneous conditions.

PMID:
26299432
PMCID:
PMC4589543
DOI:
10.1016/j.chom.2015.07.006
[Indexed for MEDLINE]
Free PMC Article

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